Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain

The ability to predict protein-ligand binding affinities is a difficult and elusive goal in the field of molecular recognition. Models exist to predict binding energetics; however, they are not always capable of considering the incidental events in ligand-binding due to the tendency of the Gibbs free energy (ΔG°) to lack a correlation with enthalpy (ΔH°), entropy (ΔS°), or both. Binding studies of various pYEEI-derived peptidomimetic ligands to the Src SH2 domain were evaluated to investigate the effects of structural changes on protein-ligand binding energetics. The effect of preorganizing the pYEEI ligand into its binding conformation was analyzed by substituting the isoleucine residue with a conformationally constrained amino acid analog as well as a flexible analog. Isothermal titration calorimetry studies were performed to assess the effects of ligand structure on protein-ligand binding energetics.

Name thesis:degree_name

Master of Arts

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Chemistry

Grantor

The University of Texas at Austin

Year dc:date.issued

2018

Author dc:creator

• Farley, Christopher Alexander

Advisor dc:contributor.advisor

• Martin, Stephen F.

• Protein-ligand interactions
• Protein-ligand binding
• Ligand preorganization

Language dc:language.iso

en

Identifier

doi:10.15781/T2X63BQ3N

OAI identifier oai:identifier

oai:repositories.lib.utexas.edu:2152/68037